The objectives of the proposed work are to provide solutions to the following problems that presently prevent human lung transplantation from being practical therapeutically: 1. What mechanisms produce lung allograft rejection? We will elucidate these mechanisms a) by performing serial correlative studies of radiographic, angiographic, and light and electron microscopic characteristics of transplanted lungs; b) by studying the vasculature of transplanted lungs with in vivo micro- observation and after making silicone rubber vascular casts; and c) by performing serial biopsies of allografted lungs and using immunofluorescent techniques to identify the localization and nature of antibody deposition. 2. How may rejection in lung grafts be identified and distinguished from other processes rapidly and safely by indirect methods? 3. How may allograft rejection be prevented safely and effectively? In this regard we will attempt to induce tolerance in animals living entirely on the function of one allotransplanted lung. We will also evaluate the value of histocompatibility matching in preventing various aspects of rejection in lung allografts. 4. What are the limits of ischemia to which a lung may be subjected and still provide adequate total pulmonary function at all times after its transplantation? These limits will be defined at various temperatures achieved with frigid gas ventilation with the hope of developing a portable lung preservation system that will permit intercontinental transportation of donor lungs. 5. What is the optimal unit of lung tissue to be transplanted in patients with bilateral pulmonary insufficiency? To resolve this question, we will transplant single lungs in animals with unilateral and bilateral experimental emphysema.